Lipoprotein Glomerulopathy, First Case Report from Canada

May combine two claims.

Only 10 cases of LPG (including this one) have been reported from North America, and previously only 5 included gene sequencing.

“Only 10 cases of LPG (including this one) have been reported from North America,2,18,21–26 and previously only 5 of these included gene sequencing: 3 APOE Kyoto,18,23 1 APOE Chicago,22 1 APOE Las Vegas.25”

• cites [2] Majeed, 2019, Can J Kidney Heal Dis sourcePartly supported

  Table 1 in the Discussion lists North American cases with APOE Kyoto, Chicago, and Las Vegas findings, supporting the claim’s general account of prior genetic testing. It lists two Kyoto cases, however, not three. The Discussion gives approximately 13 non-Asian cases worldwide, not a total of 10 North American cases or five previously sequenced North American cases. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [18] Batal, 2019, Kidney Int Rep sourcePartly supported

  The Introduction (page unavailable) says that only a few LPG cases had been described in the United States, and the Follow-up (page unavailable) reports APOE sequencing in this case. The paper does not give a total of 10 North American cases or say that five previous cases were sequenced; it also does not provide the claimed Kyoto, Chicago, and Las Vegas breakdown. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [21] Zhang, 1994, Am J Kidney Dis sourceSupported
• cites [22] Sam, 2006, Am J Kidney Dis sourceNot checked — no full text of the source
• cites [23] Rovin, 2007, N Engl J Med sourceNot checked — no full text of the source
• cites [24] Sethi, 2008, Kidney Int sourceCould not verify

  The case report (pp. 1097–1098) describes a patient with lipoprotein glomerulopathy, and its Discussion says Apo E mutations can be confirmed by DNA sequencing. It does not give a North American case count, state whether this patient was in North America, or tally previously sequenced cases (searched: North America, case count, gene sequencing, and the named APOE variants). (LLM, conf=0.74)

  Experimental — accuracy not yet measured
• cites [25] Bomback, 2010, Nephrol Dial Transplant sourceNot checked — no full text of the source
• cites [26] Boumendjel, 2010, Arch Pathol Lab Med sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Approximately 200 cases of LPG have been reported, mostly from China and Japan, with only a handful outside Asia.

“Since then, approximately 200 cases have been reported, mostly from China and Japan, with only a handful of cases reported outside of Asia.2”

• cites [2] Majeed, 2019, Can J Kidney Heal Dis sourcePartly supported

  The Discussion reports more than 150 cases, not approximately 200, so it does not establish the claimed total. It supports that most cases were from Japan and China, but its figure of approximately 13 refers to non-Asian patients, not strictly to cases reported outside Asia. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Proteins with mutations causing LPG have a tendency to aggregate.

“Studies have shown that proteins with mutations causing LPG such as APOE Sendai, APOE Chicago, APOE Osaka/Kurashiki,40 APOE Kyoto, APOE Tsukuba, and APOE Las Vegas have a tendency to aggregate.41”

• cites [40] Georgiadou, 2013, J Lipid Res sourcePartly supported

  The section “Mutations cause aggregation of apoE3 and structurally defective lipoprotein particles” reports that the three LPG-associated variants studied—Sendai, Chicago, and Osaka/Kurashiki—rapidly reached higher aggregation levels. The paper does not establish that the other variants listed in the citing sentence—Kyoto, Tsukuba, and Las Vegas—also tend to aggregate. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [41] Katsarou, 2018, J Lipid Res sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient had a previous diagnosis of dyslipidemia.

“with a previous diagnosis of dyslipidemia”

• Also stated in: § Case Report · plain

  “Another previous medical history was significant for dyslipidemia diagnosed six years ago, although he had only started taking rosuvastatin 10 mg daily 3–6 months prior.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The patient is a 49-year-old man of Chinese descent.

“A 49-year-old male of Chinese descent was found to have proteinuria with urine albumin-to-creatinine ratio (ACR) of 153.8 mg/mmol on routine laboratory testing.”

May combine two claims.

Our patient was on rosuvastatin 10 mg daily for over 6 months prior to starting fibrate therapy, and even though his lipid profile improved, his proteinuria did not.

“Our patient was on rosuvastatin 10 mg PO daily for over 6 months prior to starting fibrate therapy, and even though his lipid profile improved, his proteinuria did not.”

May combine two claims.

Our patient received four months of perindopril prior to starting fibrate therapy and proteinuria remained unchanged until fibrates were started.

“Our patient received four months of perindopril prior to starting fibrate therapy and proteinuria remained unchanged until fibrates were started.”

May combine two claims.

Renal biopsy showed markedly dilated glomerular capillaries filled with pale staining mesh-like material that stained positive for Oil-Red-O, consistent with lipoprotein thrombi.

“Renal biopsy showed markedly dilated glomerular capillaries filled with pale staining mesh-like material that stained positive for Oil-Red-O, consistent with lipoprotein thrombi.”

• Also stated in: § Case Report · plain

  “The biopsy showed that most glomeruli were enlarged and had markedly dilated capillary lumina filled with amorphous to mesh-like material that stained pale with hematoxylin and eosin, Periodic Acid Schiff, Jones’, and Masson trichrome (Figure 1A), but positive with Oil-Red-O (Figure 1B).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The patient had a new diagnosis of hypertension.

“and a new diagnosis of hypertension”

• Also stated in: § Case Report · plain

  “apart from newly diagnosed hypertension for which he had been started on perindopril 4 mg daily a week prior to his first nephrology assessment”

Probably not a substantial claim: may not pass S3 (load-bearing).

LPG was first described in Japan in 1989.

“Lipoprotein glomerulopathy (LPG) is a condition first described in Japan in 1989.1”

• Also stated in: § Discussion · plain

  “It was first reported in 1989.1”

• cites [1] Saito, 1989, Am J Kidney Dis sourceNot checked — no full text of the source

May combine two claims.

The flocculent subendothelial material is a milder morphologic manifestation of LPG and possibly a precursor in the formation of lipoprotein thrombi.

“supports the idea that this substance is a milder morphologic manifestation of this condition and possibly a precursor in the formation of lipoprotein thrombi.”

May combine two claims.

The presence of subendothelial material is a feature specific to LPG that correlates with disease severity.

“suggesting that the presence of this subendothelial material is a feature specific to LPG that correlates with disease severity.”

Probably not a substantial claim: may not pass S3 (load-bearing).

LPG is inherited in an autosomal dominant fashion with incomplete penetrance.

“It is usually caused by a mutation in apolipoprotein E (apoE) and is inherited in an autosomal dominant fashion with incomplete penetrance.3”

• cites [3] Tsimihodimos, 2011, Curr Opin Lipidol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent.

“LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent, with males more commonly affected than females.3”

• cites [3] Tsimihodimos, 2011, Curr Opin Lipidol sourceNot checked — no full text of the source

May combine two claims.

These lipoproteins then accumulate in glomeruli and form lipoprotein thrombi.

“These lipoproteins then accumulate in glomeruli and form lipoprotein thrombi.”

• cites [3] Tsimihodimos, 2011, Curr Opin Lipidol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

LPG affects males more commonly than females.

“LPG usually presents as progressively worsening proteinuria in a patient of East Asian descent, with males more commonly affected than females.3”

• cites [3] Tsimihodimos, 2011, Curr Opin Lipidol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based).

LPG is difficult to clinically differentiate from other proteinuric kidney diseases associated with dyslipidemias.

“LPG is a disease that is difficult to clinically differentiate from other proteinuric kidney diseases associated with dyslipidemias.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Patients with LPG often, but not always, have co-existent hypertriglyceridemia.

“Patients often, but not always, have co-existent hypertriglyceridemia.”

• cites [3] Tsimihodimos, 2011, Curr Opin Lipidol sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

Considering the diverse ethnic population found in Canada, and in particular the large Asian communities in Canada, it is likely that the absence of case reports of LPG represents under-diagnosis or under-reporting of this entity.

“Considering the diverse ethnic population found in Canada, and in particular the large Asian communities in Canada, it is likely that the absence of case reports of LPG represents under-diagnosis or under-reporting of this entity.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Appropriate treatment results in significant recovery, while lack of treatment can often lead to significant loss of kidney function.

“While appropriate treatment results in significant recovery, lack of treatment can often lead to significant loss of kidney function, further highlighting the importance of accurate diagnosis and appropriate treatment.”

Classified as probably not a substantial claim.

Patients with LPG are likely under-biopsied due to the presumption that their underlying kidney disease must be from more common conditions, such as hypertension, diabetes, or IgA nephropathy.

“Indeed, the clinical presentation can be very subtle and patients with this disease are likely under-biopsied due to the presumption that their underlying kidney disease must be from more common conditions, such as hypertension, diabetes, or IgA nephropathy.”

Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

Considering the diversity of population in many countries across the world, it is likely that this disease is under-recognised outside of China and Japan.

“Considering the diversity of population in many countries across the world, it is likely that this disease is under-recognised outside of China and Japan.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

There have been no cases reported of LPG that resolve spontaneously without treatment.

“There have been no cases reported of LPG that resolve spontaneously without treatment.”

May combine two claims.

Of these repeat biopsies, 20 (including this one) showed improvement or resolution of lipoprotein thrombi, and 2 cases showed no improvement.

“Of these repeat biopsies, 20 (including this one) showed improvement or resolution of lipoprotein thrombi, and 2 cases showed no improvement.”